BackgroundMetastatic germ cell tumor (mGCT) patients receiving chemotherapy have increased risk of life‐threatening venous thromboembolism (VTE). Identifying VTE risk factors may guide thromboprophylaxis in this highly curable population.MethodsData were collected from mGCT patients receiving first‐line platinum‐based chemotherapy at 22 centers. Predefined variables included International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification, long‐axis diameter of largest retroperitoneal lymph node (RPLN), Khorana score, and use of indwelling vascular access device (VAD). VTE occurring at baseline, during chemotherapy and within 90 days, was analyzed.ResultsData from 1135 patients were collected. Median age was 31 years (range 10‐74). IGCCCG risk was 64% good, 20% intermediate, and 16% poor. VTE occurred in 150 (13%) patients. RPLN >3.5 cm demonstrated highest discriminatory accuracy for VTE (AUC 0.632, P < .001) and was associated with significantly higher risk of VTE in univariable analysis (22% vs 8%, OR 3.0, P < .001) and multivariable analysis (OR 1.8, P = .02). Other significant risk factors included, Khorana score ≥3 (OR 2.6, P = .008) and VAD use (OR 2.7, P < .001).ConclusionsLarge RPLN and VAD use are independent risk factors for VTE in mGCT patients receiving chemotherapy. VAD use should be minimized in this population and thromboprophylaxis might be considered for large RPLN.

the goal of the cLoVeR study was to perform a pairwise comparison of four tests based on the same patient population with non-small cell lung cancer (NSCLC): three validated PDL1 immunohistochemistry (IHC) assays (Ventana SP142, Ventana SP263, Dako 22C3) and one PCR test. Four hundred seventy-three NSCLC samples were obtained from a biobank and were stained using PDL1 IHC assays. Four trained pathologists independently evaluated the percentage of tumor cells (TC) and immune cells (IC) that stained positive at any intensity. PDL1 transcripts were quantified in 437 patients by a standard Taqman RT-PCR assay using SDHA as a reference gene. A concordance analysis was performed to assess (1) the correlation of TC and IC between different assays and (2) the predictive properties of one test for another. "High" RNA expression was detected in 187 of 437 (43%) patients. The percentage of PDL1-positive cells (≥1%) was higher among the IC than the TC in all IHC three assays. The Pearson correlation coefficients (PCC) for TC were 0.71, 0.87, and 0.75 between 22C3/ SP142, 22C3/SP263, and SP263/SP142, respectively. The PCC for IC were 0.45, 0.61, and 0.68 for the same pairs. A low correlation was observed between the PCR test and each of the three IHC assays; however, if a patient tested low/negative by PCR, then they were likely to test negative by any single IHC test with a high probability (92-99%). Among patients who tested positive by PCR, only 9-45% tested positive by IHC assays. There was excellent positive and negative agreement (>91%) between 22C3 and SP263 staining using the recommended individual cutoffs for first-line treatment. PCR RNA expression analysis is not equivalent to IHC. However, this method may have some potential for the identification of PDL1-negative tumors. 22C3 could be considered as a substitute for SP263 in first-line treatment.In recent years, immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PDL1, CD274), have presented an alternative revolutionary therapeutic approach for patients with nonsquamous and squamous non-small-cell lung cancer (NSCLC) 1 .Pembrolizumab, an anti-PD-1 humanized antibody, is recommended as a first-line single agent for patients with metastatic NSCLC and PDL1 expression levels greater than 50% detected by immunohistochemistry (IHC) with the diagnostic antibody 22C3 (Agilent) 2,3 . Pembrolizumab was recently approved for use in the first-line One test-specific cutoff rule for each assay was pre-specified as: for first-line treatment the Tumor Proportion Score (TPS, the percentage of viable tumor cells showing partial or complete membrane staining relative to all viable tumor cells present in the sample) ≥50% for 22C3, TC or IC ≥ 5% for SP142, TC ≥ 25% for SP263, and for second-line treatment TPS ≥ 1% for 22C3, TC ≥ 50% or IC ≥ 10% for SP142, and TC ≥ 25% for SP263 (Table 1). Delta CT = 2 was conditionally chosen as the threshold between "high" ("positive") and "low/absent" ("negative") PDL1 RNA expression. ResultsPatie...

The aim of our study was to determine the effect of homologous recombination deficiency (HRD) on prognosis and efficacy of platinum-based chemotherapy in patients with pancreatic cancer (PC). We performed PubMed and Embase database queries. We included 4 studies into the meta-analysis and 16 studies in the systematic review. Our systematic analysis showed that the average weighted median overall survival (OS) in patients with HRD with advanced PC was 19.8 and 15.6 months in patients without HRD. With platinum-based chemotherapy, the average weighted median OS in patients with HRD was 23.8 and 17.1 months in patients without HRD. Without platinum-based chemotherapy, the average weighted median OS in patients with HRD was 8.3 and 12.0 months in patients without HRD. For resected PC, our meta-analysis demonstrated that HRD status did not affect the prognosis (HR 1.03, 95% CI 0.46 to 2.33), but results were rather heterogeneous (I2=83%, p=0.003). Our systematic analysis showed that the average weighted median OS in patients with HRD was 34.6 and 27.0 months in patients without HRD. With platinum-based chemotherapy, the average weighted median OS in patients with HRD was 46.1 and 36.3 months in patients without HRD. Without platinum-based chemotherapy, the average weighted median OS in patients with HRD was 24.2 and 42.9 months in patients without HRD. Results of our meta-analysis and systematic review support the idea of platinum use in patients with HRD both in resected and metastatic PCs, although a randomised trial is warranted to make a more reliable conclusion.PROSPERO registration numberCRD42019121914.

In this collaborative study by the Russian Society of Clinical Oncology and the Russian Society of Pathology, we assessed the concordance among three validated, commercially available PD-L1 immunohistochemistry assays for patients with urothelial cancer. Tumors from 100 urothelial cancer patients were stained with the antibody clones 22C3 (Agilent), SP142 (Ventana Medical Systems), and SP263 (Ventana Medical Systems), which are used in clinical trials of second-line therapy with checkpoint inhibitors. Four trained pathologists independently evaluated the percentages of tumor cells (TC) and tumor-infiltrating immune cells (IC) that were stained at any intensity by each of the antibodies. The test-specific cutoffs for the proportions of stained cells in a positive sample were pre-specified as TC + IC ≥ 10% or TC ≥ 10% for 22C3, IC ≥ 5% for SP142, and TC ≥ 25% or IC ≥ 25% for SP263. Three hundred immunohistochemistry slides were scored. The percentages of PD-L1 staining in the three assays without using any cutoff were higher in the IC than in the TC (55% versus 24% for 22C3, 45% versus 8% for SP142, and 72% versus 27% for SP263, respectively). The Pearson correlation coefficients for anti-PD-L1 staining in the IC were 0.5, 0.69, and 0.85 with 22C3/SP142, 22C3/SP263, and SP142/SP263, respectively. The Pearson correlation coefficients for PD-L1 staining in the TC were 0.93, 0.99, and 0.91 for the same pairs. Among the patients who were negative for PD-L1 staining by one test, 91-100% were also negative by the other tests. Among the patients who were positive by one test, 43-100% were also positive by the other tests. Our data indicate that repeated testing can be avoided as a patient with urothelial cancer who is classified as negative for PD-L1 expression by one of the three single tests using the corresponding cutoff rule is highly likely (91-100%) to be classified as negative by either of the other tests.

The number of patients receiving statins increases every year and due to the fact that they should take statins during their lives, the problem of their safety use comes to the forefront. The paper analyzes the safety of using the medications of this group and discusses the diagnosis of myopathies induced by statins and the occurrence of immune-mediated statin myopathies. It considers a personalized approach to prescribing statins, analyzes Russian and foreign experience in using pharmacogenetics to reduce the risk of myopathies, publishes the results of the authors' experience in clinically introducing pharmacogenetic testing at hospitals, and analyzes the long-term results of determining the polymorphism of the SLCO1B1 gene for the prediction of the risk of adverse events when using statins and estimating patient compliance to prescribed treatment.